Today’s pharmacists face both a clinical and ethical dilemma surrounding the medical use of a DEA Schedule I drug: marijuana, or specifically, one of its components, cannabidiol (CBD). Evidence-based drug information on OTC products and prescription medications with product safety guidelines have been the cornerstones of pharmacy practice. With medical marijuana use becoming commonplace in many states, pharmacists are often requested to provide patients with appropriate drug information. This has been challenging because there is limited medical-based information or documentation on cannabis. Since CBD’s introduction to the public marketplace, a plethora of misinformation has arisen based on opinion and conjecture. As of 2020, there are three CBD categories (industrial hemp-derived, marijuana-derived, and pharmaceutical-derived) that are becoming robust markets.1.Report The C.B.D. Industry Outlook. Executive Summary.Hemp Business Journal. 2018; 2018: 2-5Google Scholar States that have legalized the use of medical cannabinoids have done so for “qualifying medical uses” (Table 1).2.State Medical Marijuana Laws Key Aspects of State and D.C. Medical Marijuana Laws, from National Conference of State Legislatures.www.ncsl.orgGoogle Scholar Most of these legal changes have occurred since 2013 and have created a medical dilemma for health professionals. Depending on the state, the use of combination drugs that contain both tetrahydrocannabinol (THC) and CBD may be permitted for these specific medical conditions, whereas other states may only allow CBD-containing products. As of 2019, 33 states have approved medical marijuana state programs. An additional 13 states have allowed the use of “low THC, high CBD” for qualifying medical reasons. Figure 1 depicts the current legalized medical use of cannabis or cannabinoids, such as CBD, for each state.3.State Medical Marijuana Laws. National Conference of State Legislatures. https://www.ncsl.org/research/health/state-medical-marijuana-laws.aspx. Published March 10, 2020. Accessed June 2, 2020.Google ScholarTable 1Qualifying Medical Users of Medical MarijuanaSource: Key Aspects of State and D.C. Medical Marijuana Laws. Marijuana Policy Project. https://www.mpp.org/issues/medical-marijuana/state-by-state-medical-marijuana-laws/key-aspects-of-state-and-d-c-medical-marijuana-laws/. Accessed July 10, 2020Alzheimer’s DiseaseAnorexiaArnold-Chiari malformationArthritisAtaxiCachexiaCancerCardiopulmonary respiratory syndromeCausalgiaCervical dystoniaCrohn’s diseaseDecompensated cirrhosisDystoniaEpilepsyFibromyalgiaGlaucomaHepatitis CHIV/AIDSHuntington’s diseaseHydrocephalusInflammatory autoimmune-mediated arthritisInflammatory bowel disease (IBS)Inflammatory demyelinating polyneuropathyInterstitial cystitisLou Gehrig’s disease (amyotrophic lateral sclerosis, ALS)LupusMigrainesMultiple SclerosisMuscle spasmsMuscular dystrophyMyasthenia gravisMyoclonusNail-patella syndromeNausea or vomitingNeurofibromatosisNeuropathyPainPancreatitisParkinson’s diseasePeripheral neuropathyPost-traumatic stress disorder (PTSD)Reflex sympathetic dystrophyResidual limb pain from amputationSeizure disordersSjogren’s syndromeSpasticitySpinal cord damage with intractable spasticitySyringomyeliaTerminal illnessTourette’s syndromeTraumatic brain injury Open table in a new tab Some patient populations are demanding the use of medical marijuana for various chronic disease states, but there is a lack of medical knowledge on how to provide and improve health care with cannabinoids in these varying populations. With this direction of the expanding medical marijuana and CBD markets, pharmacists need to know the most current, evidence-based information. This will allow them to effectively counsel their patients on the appropriate uses, benefits, and risks of CBD products and medical marijuana. Accreditation informationProvider: APhATarget audience: PharmacistsRelease date: August 1, 2020Expiration date: August 1, 2023Learning level: 1ACPE Universal Activity Number: 0202-0000-20-246-H01-PCPE credit: 2 hours (0.2 CEUs)Fee: There is no fee associated with this activity for members of the American Pharmacists Association. There is a $25 fee for nonmembers. APhA is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 0202-0000-20-246-H01-P.Advisory board: Hannah Holloway, Madeline Marsh, and Minna Hassan, PharmD candidates, UGA College of Pharmacy; and Kathleen Collins, PharmD, BCPSDisclosures: Merrill Norton, PharmD, DPh, ICCDP-D, Kathleen Collins, PharmD, BCPS, Hannah Holloway, Madeline Marsh, Minna Hassan, and APhA’s editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria.Development: This home-study CPE activity was developed by APhA Learning objectives▪Summarize the differences between the three types of cannabidiol (CBD) products.▪List the dosing instructions and adverse effects of Epidiolex (cannabidiol oil).▪List the criteria for choosing a high-quality hemp derived CBD product.▪Discuss the pharmacological properties of CBD.▪Identify the benefits and risks of CBD products. Provider: APhA Target audience: Pharmacists Release date: August 1, 2020 Expiration date: August 1, 2023 Learning level: 1 ACPE Universal Activity Number: 0202-0000-20-246-H01-P CPE credit: 2 hours (0.2 CEUs) Fee: There is no fee associated with this activity for members of the American Pharmacists Association. There is a $25 fee for nonmembers. APhA is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education (CPE). The ACPE Universal Activity Number assigned to this activity by the accredited provider is 0202-0000-20-246-H01-P. Advisory board: Hannah Holloway, Madeline Marsh, and Minna Hassan, PharmD candidates, UGA College of Pharmacy; and Kathleen Collins, PharmD, BCPS Disclosures: Merrill Norton, PharmD, DPh, ICCDP-D, Kathleen Collins, PharmD, BCPS, Hannah Holloway, Madeline Marsh, Minna Hassan, and APhA’s editorial staff declare no conflicts of interest or financial interests in any product or service mentioned in this activity, including grants, employment, gifts, stock holdings, and honoraria. Development: This home-study CPE activity was developed by APhA ▪Summarize the differences between the three types of cannabidiol (CBD) products.▪List the dosing instructions and adverse effects of Epidiolex (cannabidiol oil).▪List the criteria for choosing a high-quality hemp derived CBD product.▪Discuss the pharmacological properties of CBD.▪Identify the benefits and risks of CBD products. Preassessment questionsBefore participating in this activity, test your knowledge by answering the following questions. These questions will also be part of the CPE assessment.1.Substances in Schedule I have no current accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse. DEA has changed this rule to include which CBD product to Schedule V?a.Marinolb.Cesametc.Epidiolexd.Suboxone2.FDA has approved CBD products to be placed in Schedule V if the product contains no more than ____ THC.a.1%b.5%c.0.5%d.0.1%3.Industrial hemp must contain no more than _____ concentration of THC.a.3%b.0.03%c.0.3%d.0.1% Preassessment questions Before participating in this activity, test your knowledge by answering the following questions. These questions will also be part of the CPE assessment.1.Substances in Schedule I have no current accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse. DEA has changed this rule to include which CBD product to Schedule V?a.Marinolb.Cesametc.Epidiolexd.Suboxone2.FDA has approved CBD products to be placed in Schedule V if the product contains no more than ____ THC.a.1%b.5%c.0.5%d.0.1%3.Industrial hemp must contain no more than _____ concentration of THC.a.3%b.0.03%c.0.3%d.0.1% Cannabidiol, better known as CBD, is a plant-derived compound from Cannabis sativa, the species of plant that includes both hemp and marijuana. However, these components can vary based on the different plant varieties or cultivars. CBD is the primary nonpsychoactive (noneuphoric) compound in cannabis, whereas THC is the primary psychoactive (euphoric) compound in cannabis. CBD is promoted as a possible treatment for a range of conditions such as epileptic seizures, PTSD, anxiety, and inflammation. Yet, there may be limited scientific evidence to substantiate these claims. In the United States, CBD is marketed in a range of consumer products—food and beverages, OTC supplements, personal care products, and cosmetics—that are subject to FDA regulation. Marketed consumer products containing plant-based CBD are either hemp-derived or marijuana-derived.4.Gill, LL. “CBD Goes Mainstream.” Consumer Reports. www.consumerreports.org/cbd/cbd-goes-mainstream/. Published April 11, 2019.Google Scholar CBD was first isolated in 1940 by Roger Adams, and the stereochemistry was identified by Raphael Mechoulam in 1963.5.National Academies of Sciences, Engineering, and Medicine The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. The National Academies Press, Washington, DC2017https://doi.org/10.17226/24625Crossref Google Scholar CBD does not have the intoxicating aspects of THC, and this may be due to its low affinity for the CB1 and CB2 cannabinoid receptors. It is this nonpsychoactivity that makes CBD a desirable alternative for several medical conditions.5.National Academies of Sciences, Engineering, and Medicine The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. The National Academies Press, Washington, DC2017https://doi.org/10.17226/24625Crossref Google Scholar CBD does have effects on the brain, but the exact cause of these effects is not clear. The receptor mechanisms of CBD are not known but may include effects on the nucleoside transporter; orphan G-protein-coupled receptor (GPR55); transient receptor potential of melastatin type 8 channel; 5-HT1a receptor; α3 and α1 glycine receptors; and the transient receptor potential of ankyrin type 1 channel.6.Zou S. Kumar U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System.Int J Mol Sci. 2018; 19 (Published March 13, 2018) (Accessed April 18, 2020): 833https://doi.org/10.3390/ijms19030833Crossref Scopus (360) Google Scholar, 7.Devinsky O. Cilio M.R. Cross H. et al.Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.Epilepsia. 2014; 55 (Accessed April 18, 2020): 791-802https://doi.org/10.1111/epi.12631Crossref PubMed Scopus (515) Google Scholar Specifically, there are three pharmacological targets that have been identified to have an affinity to modulate neuronal excitability, transient receptor potential vanilloid 1 (TRVP-1), G protein-coupled receptor 55 (GPR55), and equilibrative nucleoside transporter 1 (ENT-1). These targets may play a role in the possible mechanisms of action of CBD in epilepsy.7.Devinsky O. Cilio M.R. Cross H. et al.Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.Epilepsia. 2014; 55 (Accessed April 18, 2020): 791-802https://doi.org/10.1111/epi.12631Crossref PubMed Scopus (515) Google Scholar Another potential mechanism of action of CBD is the ability of this compound to potentiate glycine receptors (GlyRs) in order to produce an analgesic effect without significant psychoactive side effects. CBD is extensively metabolized in the liver with a number of metabolites being excreted in the urine and feces. There are at least seven CYP450 enzymes capable of metabolizing CBD: CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 (Figure 2).9.Brown J.D. Winterstein A.G. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use.J Clin Med. 2019; 8 (Published July 8, 2019): 989https://doi.org/10.3390/jcm8070989Crossref Scopus (77) Google Scholar As a result of these interactions, a synergistic pharmacodynamic drug–drug interaction (DDI) may occur, which affects CBD in patients with existing serious medical conditions such as epilepsy and multiple sclerosis.9.Brown J.D. Winterstein A.G. Potential Adverse Drug Events and Drug-Drug Interactions with Medical and Consumer Cannabidiol (CBD) Use.J Clin Med. 2019; 8 (Published July 8, 2019): 989https://doi.org/10.3390/jcm8070989Crossref Scopus (77) Google Scholar In order to understand the complex and constantly evolving role of CBD in today’s society, it is important to grasp a more macroscopic view of the legalities surrounding the sources of CBD. In 2018, the United States Congress elucidated on the current governing definition of hemp with an amendment to the 2014 Farm Bill. The new bill, stated in section 297A of the Agricultural Marketing Act of 1946, defines “hemp” as a derivative of the Cannabis sativa plant that contains no more than 0.3% concentration on a dry weight basis of delta-9-tetrahydrocannabinol, or THC.10.Johnson R. Defining Hemp: A Fact Sheet.Congressional Research Service. 2019; : 1-4Google Scholar As a result, “marijuana” is defined as anything above that specified threshold with no definite limit to the amount of THC. This expansion, in efforts to decrease restriction on research, allowed the governing bodies to draw a distinction between marijuana and hemp. The Agriculture Improvement Act of 2018, referred to as the 2018 Farm Bill, excluded industrial hemp from the Controlled Substances Act (CSA) and removed hemp from the CSA definition of marijuana. This legislation authorized interstate commerce of hemp-derived products and established a framework of hemp production by the United States Department of Agriculture (USDA) pursuant to USDA-administered plans or USDA-approved state plans. FDA keeps the authority for oversight of all hemp-derived products under the Food, Drug, and Cosmetic Act (FDCA) concerning claims of therapeutic benefits of unapproved products. FDA states “disease claims are not permitted for dietary supplements, food, or cosmetics,” elucidating that hemp is legal in the United States with serious restrictions.16.Jeliazekov V.D. et al.What Is Industrial Hemp? Oregon State University Extension Service. EM 9240.2019Google Scholar Once hemp was removed from CSA and was no longer considered controlled, a variety of federal changes regarding research, development, and regulatory oversight took place. In a directive released by the Drug Enforcement Administration (DEA), products that contained CBD that had less than 0.3% THC were able to be sold and distributed without regulation under the CSA. Yet, there was a stipulation that it must be produced by an authorized grower and meet applicable state regulations. This allowed hemp-derived products to be legally produced and marketed to the public.11.Hudak J. The Farm Bill, hemp legalization and the status of CBD: An explainer. Brookings. https://www.brookings.edu/blog/fixgov/2018/12/14/the-farm-bill-hemp-and-cbd-explainer/. Published December 13, 2018. Accessed April 18, 2020.Google Scholar The 2018 Farm Bill, with its creation of hemp as a federal crop, had an impact on the administrative side of crop cultivation as well. States were now prohibited from impeding or interfering with the transport of hemp products that met the new USDA standards.12.Johnson R. Farm Bill Primer: Hemp Cultivation and Processing. Congressional Research Service. Published, 2018: 2019Google Scholar It is important to note that while all these changes in hemp classification have occurred, marijuana and other cannabinoids are still currently considered a Schedule I substance. Therefore, marijuana and cannabinoid products are still under strict regulation of CSA and DEA and are not for legal production. In comparison to hemp, THC levels for these products can average anywhere between 10% to 30%.10.Johnson R. Defining Hemp: A Fact Sheet.Congressional Research Service. 2019; : 1-4Google Scholar However, with advancements in cultivation and breeding, many strains and subspecies of cannabis have been shown to have higher levels. Listed in the Title Code 21 of the CSA as a Schedule I substance, cannabis does not currently have an accepted medical use, lacks safety for use under medical supervision, and has a substantial potential for abuse.13.Drug Enforcement Administration Pharmacist’s Manual an Informational Outline of the Controlled Substances Act. United States Department of Justice Office of Diversion Control, 2010Google Scholar There have been many attempts to reschedule cannabis from a Schedule I to another classification in the CSA. The latest attempt, in August 2016, resulted in DEA reporting there was not sufficient evidence to remove cannabis from its current ranking.14.DEPARTMENT OF JUSTICE Drug Enforcement Administration 21 CFR Chapter II [Docket No. DEA–427] Denial of Petition to Initiate Proceedings to Reschedule Marijuana Federal Register.81. 2016: 156Google Scholar Regardless of whether the substance is hemp-derived or marijuana-derived, FDA maintains that any product containing CBD or other cannabinoids cannot be marketed for food or as dietary supplements. It also states products should not make any therapeutic claims that have not been approved prior by FDA.10.Johnson R. Defining Hemp: A Fact Sheet.Congressional Research Service. 2019; : 1-4Google Scholar This statement has led to many sellers of CBD receiving warning letters from FDA for unlawful production or marketing of unsubstantiated health claims. FDA, heeding the warnings of unlawful products entering the market, has created and reopened a forum for stakeholders to make submissions regarding these types of developments, indicating that the public can also play a role in submitting data surrounding lawful and unlawful CBD products on the market today. One particularly complex area of legalities surrounds the production and sale of consumable cannabis products, or edibles. An “edible” or “medible,” is a cannabis-infused product meant for human consumption. This can come in a variety of forms such as gummies or homemade goods. There is speculation about the legality of these sales because currently FDCA prohibits the introduction of food items containing added CBD to the market for interstate commerce.15.Flint D.L. Shelton D.M. Cannabis-Derived Botanical Drugs: A Viable regulatory pathway for marketing medical edibles?.2019: 118-224Google Scholar This provision, by definition of interstate commerce, prohibits the sale of any food or dietary supplement containing CBD that crosses state boundaries or involves more than one state. States like Maine, Ohio, and New York have already taken the initiative to ban the sale of edibles, but many states have not. Those who continue to sell edibles do so regardless of whether FDA truly has authority to prohibit sale. Recently, FDA has withheld any attempts to regulate the sale of edibles. In 2017, FDA issued warning letters to multiple vendors citing FDCA.15.Flint D.L. Shelton D.M. Cannabis-Derived Botanical Drugs: A Viable regulatory pathway for marketing medical edibles?.2019: 118-224Google Scholar This gray area will continue to change and adapt as the laws surrounding CBD production change, so it is important to stay up to date about your specific state’s laws and regulations regarding these complex matters. Despite these ever-changing classifications and regulations, on June 25, 2018, FDA announced it approved the first CBD drug called Epidiolex. This drug is nonsynthetic, a CBD oil isolate, extracted directly from the cannabis plant, and only contains purified CBD. It is currently approved to treat seizures that result from Lennox-Gastaut syndrome and Dravet syndrome in patients older than 2 years. Due to its established medical utility, Epidiolex is not classified as a Schedule I in the CSA. The progression of this drug through the stringent drug approval process may serve as a catalyst of its own and for other cannabis-derived products. The three categories of CBD are distinctly different in several ways. Industrial hemp-derived CBD is just one of many different types of products that are derived from the industrial hemp plant. Other products produced from the plant are food items, building materials, and fiber products for paper, jewelry, and rope. Marijuana-derived CBD differs from industrial hemp-derived CBD primarily by the amount of THC in the product and how each state regulates the medical use of the product. Pharmaceutical-derived CBD is an approved drug by FDA and is available nationally. In 2019, 48 states and Puerto Rico considered more than 200 bills related to industrial hemp-derived CBD production and regulation. At least six of those states—Connecticut, Georgia, Louisiana, Iowa, Ohio, and Texas—enacted legislation to establish state programs. South Dakota passed House Bill 1191, legalizing the growth and production of industrial hemp, which was ultimately vetoed by the governor. Other states, such as Florida, Kansas, Oklahoma, and Maryland, enacted legislation to expand or rename existing programs. New Hampshire created its own study committee centered around the legalities and logistics of growing hemp (House Bill 459). Mississippi also created a task force to study the cultivation of hemp (House Bill 1547).17.National Conferences of State Legislatures The NCSL Podcast.April 16, 2020Google Scholar USDA established the Domestic Hemp Production Program in October 2019, which outlines the regulated provisions for the agricultural business of producing industrial hemp.18.Federal Register Establishment of a Domestic Hemp Production Program. 84 FR 58522.October 31, 2019Google Scholar Industrial hemp is considered a low-maintenance crop. This means once planted, hemp plants require little attention to produce significant yields. On average, a cultivated industrial hemp plant, consisting of spindly stalk and leaves, can grow to be 10 feet or higher in height. As for time, it can take anywhere between 70 to 140 days for the plants to be harvested. The number of days can depend on a variety of factors, such as the intended purpose of the crop, the location, and the climate in which it is grown. Hemp is often grown to create a variety of things. Typically, “1 acre of hemp can yield an average of 700 pounds of grain, which in turn can be pressed into about 22 gallons of oil and 530 pounds of meal. … The same acre will also produce an average of 5,300 pounds of straw, which can be transformed into approximately 1,300 pounds of fiber.”19.Callaway J.C. Hempseed as a nutritional resource: an overview.Euphytica. 2004; 140: 65-72Crossref Scopus (419) Google Scholar Industrial hemp’s CBD oil is derived from the stalk, stems, leaves, and flowers of the hemp plant. The only part of the hemp plant that does not contain CBD oil is the seed.19.Callaway J.C. Hempseed as a nutritional resource: an overview.Euphytica. 2004; 140: 65-72Crossref Scopus (419) Google Scholar CBD oil can be found in a variety of products such as body lotions, tinctures, and capsules. The market for these products is expanding, with the CBD industry expected to grow to $22 billion by 2022, a drastic increase from $327 million in 2017.18.Federal Register Establishment of a Domestic Hemp Production Program. 84 FR 58522.October 31, 2019Google Scholar This type of growth is making many producers eager to join the industry and develop new products. However, this rapid growth comes with the need for increased scrutiny of these products. It is crucial to ensure that companies selling CBD products are using industrial hemp extract along with carrier oils that have been grown and processed in ways that are healthy for consumers and the environment. Companies should be transparent about their production practices in the labeling and advertising of these products.20.Hall W. A summary of reviews of evidence on efficacy and safety of medical use of cannabis and cannabinoids. University of Queensland. Published, December 2018Google Scholar The main difference between CBD oil from industrial hemp versus marijuana is the ratio between THC and CBD. Industrial hemp-derived CBD oil usually contains high concentrations of CBD, while its THC content does not exceed the legal 0.3% limit. Marijuana-derived CBD oil is sourced from selectively bred high-CBD strains, but it also comes with significant amounts of THC (ranging between 5% and 30%). Marijuana-derived CBD oil is extracted from marijuana plants that have thick, lush foliage and flowers that are generally grown and consumed for their intoxicating properties. While most marijuana plants contain THC as the predominant cannabinoid, there are several strains of marijuana that are rich in CBD oil. A critical difference between industrial hemp-derived CBD oil and marijuana-derived CBD oil is the resin content of each plant. Cannabis resin is found within the trichomes of buds and, to a lesser extent, on the leaves. Marijuana plants usually contain copious amounts of resin, while industrial hemp plants contain significantly less. Marijuana offers a more abundant source of CBD oil than hemp, thus the extraction of CBD oil from industrial hemp plants requires a larger quantity.10.Johnson R. Defining Hemp: A Fact Sheet.Congressional Research Service. 2019; : 1-4Google Scholar States license a finite number of pharmaceutical processors to cultivate and distribute marijuana-derived CBD oil. The number of pharmaceutical processors that can be licensed varies from state to state. In states without legalized recreational marijuana, pharmaceutical processors are permitted to distribute marijuana-derived CBD oil to patients who have obtained a valid written certification from a state registered physician with the state medical, pharmacy, or health boards. Registered physicians may issue certifications to patients if they determine the patient will medically benefit from marijuana-derived CBD oil. In some states, registered physician assistants and nurse practitioners may also issue certifications. State regulations also allow for the legal possession of marijuana-derived CBD oil for individuals with valid written certifications. The law provides an affirmative defense for these patients if they are criminally charged with possession of the substance. An affirmative defense in this circumstance would require the defendant to produce evidence that they have a written certification from an approved practitioner. All products classified as marijuana remain illegal under federal law. 21.Carlton J. The Legality and Availability of CBD Oil in Virginia, Issue Brief. Virginia Division of Legislative Services.2019Google Scholar Since 1985, FDA has licensed four drugs based on cannabinoids. First is dronabinol, the generic name for synthetic Delta 9-THC, which is marketed under the trade name of Marinol. It is clinically indicated to counteract the nausea and vomiting associated with chemotherapy and to stimulate appetite in patients with AIDS affected by cachexia, or wasting syndrome. Nabilone (Cesamet), which is a synthetic analog of Delta 9-THC, is another drug that is prescribed for similar indications. Both dronabinol and nabilone are given orally and have a slow onset of action. Syndros was approved in 2016. It is a liquid formulation of dronabinol, for the treatment of patients experiencing chemotherapy-induced nausea and vomiting who have not responded to conventional antiemetic therapies. This agent is also indicated for treating anorexia associated with weight loss in patients with AIDS. Two additional cannabinoid-based medications have been examined by FDA. Nabiximols (Sativex) is an ethanol cannabis extract composed of delta 9 THC and CBD in a one-to-one ratio. Sativex is administered as an oral-mucosal spray and is indicated in the symptomatic relief of multiple sclerosis and as an adjunctive analgesic treatment in cancer patients. As of September 2016, Nabiximols has been launched in 15 countries, including Canada, Germany, Italy, Spain, and the United Kingdom, and has been approved in an additional 12 countries, but not in the United States.5.National Academies of Sciences, Engineering, and Medicine The health effects of cannabis and cannabinoids: The current state of evidence and recommendations for research. The National Academies Press, Washington, DC2017https://doi.org/10.17226/24625Crossref Google Scholar In 2013, in response to the urgent need expressed by parents of children with intractable epilepsy, FDA allowed investigational new drug studies of a second medication, Epidiolex, a concentrated CBD oil (>98 percent CBD), as an antiseizure medication for Dravet and Lennox-Gastaut syndromes.4.Gill, LL. “CBD Goes Mainstream.” Consumer Reports. www.consumerreports.org/cbd/cbd-goes-mainstream/. Published April 11, 2019.Google Scholar Epidiolex was FDA approved on June 25, 2018, and on September 28, 2018, DEA rescheduled FDA-approved drugs containing CBD derived from cannabis with no more than 0.1% THC in Schedule V. Consensus estimates expect sales of $1.7 billion in 2024, which would make it the largest cannabis-related, FDA-approved drug in history (it is also the first plant-based cannabinoid to gain approval).22.FDA Newsletter FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy.2018Google Scholar Epidiolex’s effectivenes